The present invention relates to diffusion cells for determining the rate of movement of chemical compounds through natural or synthetic membranes.
In the development of skin-applied drugs, it is desirable to determine the rate at which the drugs, such as systemically bioactive agents, will be absorbed through the human skin. This percutaneous absorption determination can be at least closely approximated through the use of conventional diffusion cells in which a membrane is employed which has absorption characteristics closely paralleling those of living human skin. One conventional type of diffusion cell is depicted in FIG. 8 and basically comprises chambers 1, 2 located on opposite sides of the membrane 3. One chamber 1, i.e., a so-called donor chamber 1 is adapted to receive a dose 4 of the chemical substance under study. The study substance 4 is absorbed through the membrane and enters the other cell 2, i.e., a so-called receptor cell 2. The receptor cell contains a receptor or bathing fluid such as an aqueous solution into which the study substance enters. The receptor fluid is maintained at a constant temperature by thermostatically controlled fluid which circulates through a jacket 5 surrounding the receptor chamber. The receptor fluid bathes the underside of the membrane to closely approximate the condition of living skin tissue. Introduction and removal of the receptor fluid with respect to the receptor chamber is effected through an injection port 6. The receptor fluid is periodically sampled and assayed to determine the concentration of the study substance therein. From that data, the rate of absorption of the study substance can be determined.
A homogenous distribution of the study substance in the receptor fluid is established by means of a stirring bar 7 located in the receptor chamber. The stirring bar is formed of a Teflon-coated magnetic material which is rotated by means of a motor-driven external magnet 8.
The donor chamber is formed by a cell cap 9 which is suitably clamped to the cell body 9A. An O-ring (not shown) is disposed between the cell cap and cell body to effect a fluid seal therebetween.
A shortcoming of the above-described cell involves the inconvenience and time expenditure involved in periodically removing quantities of the receptor fluid for analysis, the removal usually performed manually by means of a syringe.
Another conventional type of diffusion cell is depicted in FIG. 9. That cell is basically similar to the afore-discussed cell in that it comprises a cell body 1A, a cell cap 2A, and a water jacket 3A. A magnetic stirrer (not shown) is disposed in a lower bulbous region 1B of the cell body to which receptor fluid is introduced. Introduction and removal of the receptor fluid is usually acheived by means of a peristaltic pump 4A which is connected to a lower inlet port 5A or an upper outlet port 6A of the receptor cell by means of a flexible tube 7A. Receptor fluid is pumped from the receptor cell to a detector 8A such as a spectrophotometer and from the detector to the inlet port of the receptor cell. The detector provides an essentially continuous monitoring of the receptor fluid, which eliminates the need for the periodic manual removal of the receptor fluid. The peristaltic pump, however, requires the use of flexible tubing which typically contains components, such as plasticizers for example, which can be undesirably desorbed into the receptor fluid. Also, the tubing may absorb some of the study substance thereby adversely affecting the accuracy of the measurements.
It is, therefore, an object of the present invention to minimize or obviate shortcomings of the type discussed above.
Another object is to enable a monitoring of the reactor fluid to be effected without the risk of undesirable materials being desorbed from the tubing into the receptor fluid and without the risk of the study substance being absorbed by the tubing.
A further object is to provide a diffusion cell in which a magnetically driven bar performs both a stirring action and a pumping action, whereby a monitoring can be achieved without the use of a separate pump.